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SLC39A14 Gene Solute Carrier Family 39 Member 14

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SLC39A14 Gene Solute Carrier Family 39 Member 14 SLC39A14 gene solute carrier family 39 member 14 Normal Function The SLC39A14 gene provides instructions for making a protein that transports the element manganese across cell membranes. Manganese is important for many cellular functions, but large amounts are toxic, particularly to brain cells. The SLC39A14 protein is found in the membranes surrounding several types of cells, as well as in the membranes of structures within these cells. The protein is thought to transport excess manganese from the blood into liver cells so that it can be removed from the body through bile. Bile is a substance produced by the liver that is important for digestion and the removal of waste products. The SLC39A14 protein may also transport other elements, including zinc, iron, and cadmium, across cell membranes. The importance of this transport in the body is not well understood. Health Conditions Related to Genetic Changes Hypermanganesemia with dystonia At least five SLC39A14 gene mutations have been found to cause hypermanganesemia with dystonia 2, a condition that begins in early childhood and is characterized by high levels of manganese in the blood and brain (hypermanganesemia), involuntary tensing of the muscles (dystonia), and other movement problems. These mutations impair the transport of manganese into liver cells. As a result, the element cannot be removed from the body through bile. The excess manganese builds up in the blood and subsequently in brain cells, particularly cells in a region of the brain that helps control movement. High levels of manganese damage these cells, causing neurological problems that make controlling movement difficult. Other Names for This Gene • cig19 • HMNDYT2 • KIAA0062 • LIV-1 subfamily of ZIP zinc transporter 4 Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1 • LZT-Hs4 • NET34 • solute carrier family 39 (metal ion transporter), member 14 • solute carrier family 39 (zinc transporter), member 14 • ZIP14 • zrt- and Irt-like protein 14 • Zrt-, Irt-like protein 14 Additional Information & Resources Tests Listed in the Genetic Testing Registry • Tests of SLC39A14 (https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=23516[geneid] ) Scientific Articles on PubMed • PubMed (https://pubmed.ncbi.nlm.nih.gov/?term=%28%28SLC39A14%5BTIAB%5 D%29+OR+%28solute+carrier+family+39+member+14%5BTIAB%5D%29%29+OR+ %28%28LIV-1+subfamily+of+ZIP+zinc+transporter+4%5BTIAB%5D%29+OR+%28Z IP14%5BTIAB%5D%29+OR+%28Zrt-,+Irt-like+protein+14%5BTIAB%5D%29+OR+ %28solute+carrier+family+39++,+member+14%5BTIAB%5D%29+OR+%28zrt-+and +Irt-like+protein+14%5BTIAB%5D%29%29+AND+%28%28Genes%5BMH%5D%29 +OR+%28Genetic+Phenomena%5BMH%5D%29%29+AND+english%5Bla%5D+AN D+human%5Bmh%5D+AND+%22last+3600+days%22%5Bdp%5D) Catalog of Genes and Diseases from OMIM • SOLUTE CARRIER FAMILY 39 (ZINC TRANSPORTER), MEMBER 14 (https://omi m.org/entry/608736) Research Resources • ClinVar (https://www.ncbi.nlm.nih.gov/clinvar?term=SLC39A14[gene]) • NCBI Gene (https://www.ncbi.nlm.nih.gov/gene/23516) References • Aydemir TB, Kim MH, Kim J, Colon-Perez LM, Banan G, Mareci TH, Febo M, CousinsRJ. Metal Transporter Zip14 (Slc39a14) Deletion in Mice Increases ManganeseDeposition and Produces Neurotoxic Signatures and Diminished Motor Activity. JNeurosci. 2017 Jun 21;37(25):5996-6006. doi: 10.1523/JNEUROSCI.0285- Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 2 17.2017. Epub2017 May 23. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/28 536273) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/article s/PMC5481939/) • Chen P, Chakraborty S, Mukhopadhyay S, Lee E, Paoliello MM, Bowman AB, AschnerM. Manganese homeostasis in the nervous system. J Neurochem. 2015Aug; 134(4):601-10. doi: 10.1111/jnc.13170. Epub 2015 Jun 16. Review. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/25982296) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516557/) • Liuzzi JP, Aydemir F, Nam H, Knutson MD, Cousins RJ. Zip14 (Slc39a14) mediatesnon-transferrin-bound iron uptake into cells. Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13612-7. Epub 2006 Sep 1. Citation on PubMed (https://pubm ed.ncbi.nlm.nih.gov/16950869) or Free article on PubMed Central (https://www.ncbi. nlm.nih.gov/pmc/articles/PMC1564235/) • Mukhopadhyay S. Familial manganese-induced neurotoxicity due to mutations inSLC30A10 or SLC39A14. Neurotoxicology. 2018 Jan;64:278-283. doi:10.1016/j. neuro.2017.07.030. Epub 2017 Aug 5. Review. Citation on PubMed (https://pubmed. ncbi.nlm.nih.gov/28789954) • Taylor KM, Morgan HE, Johnson A, Nicholson RI. Structure-function analysis of a novel member of the LIV-1 subfamily of zinc transporters, ZIP14. FEBS Lett.2005 Jan 17;579(2):427-32. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/156423 54) • Tuschl K, Meyer E, Valdivia LE, Zhao N, Dadswell C, Abdul-Sada A, Hung CY, Simpson MA, Chong WK, Jacques TS, Woltjer RL, Eaton S, Gregory A, Sanford L, KaraE, Houlden H, Cuno SM, Prokisch H, Valletta L, Tiranti V, Younis R, Maher ER, Spencer J, Straatman-Iwanowska A, Gissen P, Selim LA, Pintos-Morell G,Coroleu- Lletget W, Mohammad SS, Yoganathan S, Dale RC, Thomas M, Rihel J, BodamerOA, Enns CA, Hayflick SJ, Clayton PT, Mills PB, Kurian MA, Wilson SW. Mutationsin SLC39A14 disrupt manganese homeostasis and cause childhood- onsetparkinsonism-dystonia. Nat Commun. 2016 May 27;7:11601. doi: 10.1038/ ncomms11601. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/27231142) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC489 4980/) • Xin Y, Gao H, Wang J, Qiang Y, Imam MU, Li Y, Wang J, Zhang R, Zhang H, Yu Y, Wang H, Luo H, Shi C, Xu Y, Hojyo S, Fukada T, Min J, Wang F. Manganesetransporter Slc39a14 deficiency revealed its key role in maintaining manganesehomeostasis in mice. Cell Discov. 2017 Jul 18;3:17025. doi:10.1038/ celldisc.2017.25. eCollection 2017. Citation on PubMed (https://pubmed.ncbi.nlm.nih .gov/28751976) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pm c/articles/PMC5519003/) Genomic Location The SLC39A14 gene is found on chromosome 8 (https://medlineplus.gov/genetics/chro mosome/8/). Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 3 Page last updated on 18 August 2020 Page last reviewed: 1 October 2017 Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 4.
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